Chapter 7 - Na, K, Ca

• Alkaline (Na+ and K+) and alkaline earth metal ions (Ca2+ and Mg2+) play a pivotal role in many physiological processes.
• Balance of intra- and extracellular concentration of Ca2+, K+ and Na+ is necessary for proper regulatory function.
• Balance is typically maintained by ion channels.
• Na+K+ATPase is a type of active transport that uses ATP to move ions across a membrane.
• There are four types of ion transport: Na+K+ATPase, Na+, K+, Cl−, and Ca2+/H+ exchanger.
• Na+, K+, Cl−, and Ca2+/H+ exchanger are types of passive transport that do not use ATP to move ions across a membrane.
• Trans-membrane proteins form channels.
• Ion channels can be gated by mechanical, electrical or chemical stimuli.
• Ion channels that pump against the concentration gradients (ion pumps) are powered by ATP hydrolysis.
• Alkaline (Na+ and K+) and alkaline earth metal ions (Ca2+ and Mg2+) are important for regulation of membrane potentials, information transfer by migration along concentration and/or electrochemical gradients, signal transduction, activation and regulation of enzymes, co-activation of phosphate-dependent metabolic and catabolic paths, and stabilization/activation of hydrolysis of ATP.
• The maintenance of a ‘correct’ balance of ion concentration in the intra- and extracellular space is required for physiological functions to be maintained.
• Ion channels have filters for selectivity.
• During transport the a sub-unit switches between two conformations: E1 – Na+ sensitive and E2 – K+ sensitive.
• Need efficient and specific transport facilities for cations.
• Abrupt changes cause electrical potentials responsible for transmission of nerve impulses.
• The maintenance of these imbalances requires energy.
• Conversely, the opposite gradient (~30x) must be maintained for the K+ ion.
• Potassium channels are hundreds to thousands of times more permeable to potassium than to sodium.
• The Na+ ion concentration within animal cells must be kept ~10x lower than in the extracellular fluids.
• β sub-unit anchors the pump in the membrane.
• Na+K+ ATPase is a membrane bound pump where ATP is linked to two trans-membrane glycoprotein subunits α and β.
• Na+K+ATPase is used to pump the ions against the gradient.
• α is the larger sub-unit and is the transport protein.
• Binding to ions is provided by side-chain hydroxyls (Thr, Ser) and carboxylates (Asp, Glu).
• The energy required for transport is provided by hydrolysis of a Mg-activated ATP: Mg-ATP + H2O ➞ Mg-ADP + Pi.
• Ion must "give up" its water of hydration to pass through the pore.
• The filter doesn’t allow hydrated sodium or potassium to pass through.
• Valinomycin, Nonactin, and Monensin are examples of ionophores.
• Valinomycin is an electrogenic K+ transporter, meaning transport is coupled to other processes such as anion symport or cation antiport.
• Ionophores are typically synthesised by bacteria and fungi.
• Valinomycin has a 36-membered ring and its stability constant, K, is 106 M-1.
• Calcium is generally complexed to side-chain carboxyl groups of proteins with additional interactions with carbonyl (C=O) & hydroxy (OH) groups.
• The nonpolar hydrophobic exterior groups of ionophores enable the complexes to cross cell boundaries.
• Ionophores are usually macrocyclic with oxygen donor atoms for specific binding of Na+ or K+ and polar interior groups for binding the ions.
• Calcium is essential to the action of extracellular enzymes and many regulatory processes.
• Typically a hormonal or electrical extracellular stimulus will trigger an influx of Ca2+ into the cell.
• Sodium and Potassium can cross the hydrophobic membrane via ionophores.
• Calcium often acts as a messenger in response to an external (primary) signal.
• Bones are 50% collagen and 50% hydroxyapatite.
• Monensin is an acyclic transporter for Na+ and is electro-neutral.